Rodney J. Taylor

Evaluation of cardiovascular risk for renal transplantation in diabetic patients

Abstract Cardiovascular disease contributes in a major way to morbidity and mortality in diabetic patients with end-stage renal disease. Sixty patients with type I diabetes were evaluated prior to renal transplantation to determine the risk of cardiovascular complications. On the basis of results of thallium stress testing and/or cardiac catheterization, each patient was assigned to one of five categories. There were no cardio-vascular events in the seven patients who had negative results on stress testing. Of the remaining 53 patients, all of whom underwent cardiac catheterization, 30 had normal coronary arteries. None of these 30 patients had any cardiac morbidity, and the two deaths that occurred in this group were not attributable to cardiac causes. Significant coronary artery disease was present in 38 percent of the patients. The overall mortality rate was 5.4 percent in those patients without coronary artery disease and 43.5 percent in those with the disease. In addition, the mortality rate in patients with coronary disease classified as severe was 62 percent, whereas it was 20 percent in those categorized as having moderate disease. The data indicate that patients with diabetes and end-stage renal disease who are at highest risk for cardiovascular events can be identified, and these patients probably should not undergo renal transplantation.

Cyclosporine kinetics in renal transplantation

The pharmacokinetics of cyclosporine were evaluated in 41 recipients of a cadaveric renal transplant. Cyclosporine was taken by mouth (mean dose 14 mg/kg) on one study day and was intravenously infused over 2 hours (mean dose 4.7 mg/kg) on the next study day. Cyclosporine was extracted from whole blood and analyzed by HPLC. After intravenous infusion, cyclosporine exhibited multicompartmental behavior. The mean (± SD) terminal disposition rate constant was 0.065 ± 0.036 hours−1 and the harmonic mean t½ was 10.7 hours. The harmonic mean total body clearance of cyclosporine was 5.73 ml/min/kg and the mean apparent volume of distribution was 4.5 ± 3.6 L/kg. The absorption of oral cyclosporine was slow and incomplete. Peak blood cyclosporine concentrations (X̄ = 1,103 ng/ml) were reached between 1 and 8 hours after oral dosing (X̄ = 4 hours). The mean relative bioavailability was 27.6% ± 20%. Oral bioavailability was <10% in 17% of our subjects. The absorption and clearance of cyclosporine were highly variable. We conclude that the variability in the kinetics of cyclosporine makes trough blood level monitoring essential in the management of patients who receive renal transplants.

The effect of food on cyclosporine absorption

The effect of food on the absorption of cyclosporine was evaluated in 18 recipients of cadaveric renal transplants. Cyclosporine was administered orally with a standard hospital breakfast on one study day and without breakfast on the alternate study day. The oral absorption rate as measured by the observed time to peak concentration was not significantly altered by food. The administration of cyclosporine with food resulted in a significant increase in the peak (1465 ng/ml versus 1120 ng/ml) and trough (267 ng/ml versus 228 ng/ml) blood concentrations as well as the area under the blood concentration versus time curve (11430 ng . hr/ml versus 7881 ng . hr/ml). The mean increase in area under the blood concentration versus time curve was 60.6%. The exact mechanism by which food increases the absorption of cyclosporine is not known. Regardless of the mechanism involved, if adequate immunosuppression is achieved with lower doses of cyclosporine taken with food, significant cost savings could be realized.

Opportunistic Lung Infections in Renal Transplant Patients: A Comparison of Pittsburgh Pneumonia Agent and Legionnaires’ Disease

From July 1977 to January 1980, 5 cases of pneumonia owing to Pittsburgh pneumonia agent and 4 cases owing to Legionella pneumophila occurred in our renal transplant population. Comparison of the clinical manifestations, laboratory features an radiographic changes demonstrated no unique characteristics that allowed differentiation from other bacterial pneumonias. Diagnosis in all cases required histologic or serologic identification of the infecting organism. We herein present our protocol for establishing rapidly the diagnosis of pneumonia in renal transplant patients with emphasis on the use of open lung biopsy.

Evaluation of Cardiovascular Risk for Renal Transplantation in Diabetic Patients

Cardiovascular disease contributes in a major way to morbidity and mortality in diabetic patients with end-stage renal disease. Sixty patients with type I diabetes were evaluated prior to renal transplantation to determine the risk of cardiovascular complications. On the basis of results of thallium stress testing and/or cardiac catheterization, each patient was assigned to one of five categories. There were no cardiovascular events in the seven patients who had negative results on stress testing. Of the remaining 53 patients, all of whom underwent cardiac catheterization, 30 had normal coronary arteries. None of these 30 patients had any cardiac morbidity, and the two deaths that occurred in this group were not attributable to cardiac causes. Significant coronary artery disease was present in 38 percent of the patients. The overall mortality rate was 5.4 percent in those patients without coronary artery disease and 43.5 percent in those with the disease. In addition, the mortality rate in patients with coronary disease classified as severe was 62 percent, whereas it was 20 percent in those categorized as having moderate disease. The data indicate that patients with diabetes and end-stage renal disease who are at highest risk for cardiovascular events can be identified, and these patients probably should not undergo renal transplantation.

Sternotomy and portal triad division for cadaver donor nephrectomy

Modification of the en bloc resection of kidneys for cadaveric kidney transplant patient is described. A median sternotomy and division of the portal triad provide excellent exposure of the upper aorta above the celiac axis. This approach has been used in 40 cadaveric donors with no complications.

Use and abuse of retrograde pyelography

Retrograde pyelography to demonstrate the renal pelvis and ureters is a common urologic procedure. Newer contrast materials and better radiographic techniques have obviated many of the previous indications for retrograde studies were independently reviewed by two urologists and a radiologist to determine if the studies were indicated, appropriately timed, informative, and complete. Our results indicate a high percentage of these examinations are incompletely performed and uninformative and could have been replaced by noninvasive studies. What constitutes a complete retrograde study and when to utilize this examination is discussed.